Many semisynthetic, therapeutically used cephalosponrns generally consist of 7β-acylamido-3-(substituted)methyl-3-cephem-4-carboxylic acid derivatives in which the 3-methyl group is substituted with the residue of a nucleophilic compound and the acyl group is a variously 2-mono-, 2,2-di- or 2,2,2-tri-substituted acetic acid. Mainly, the residue of the nucleophilic compound is a methoxy; acetoxy; carbamoyl; an optionally substituted heterocycle radical, including tertiary ammonium heterocycles forming an inner salt with the cephem-4-carboxylic acid, such as 5-methyltetrazol-2-yl, 1-pyridinio, 4-carbamoyl-1-pyridinio, 2-sulfoethyl-1-pyridinio, 5,6,7,8-tetrahydro-1-quinolinio, 1-cyclopentano[b]pyridinio, 1H-imidazo [1,2-b]-4-pyridazinio, 5-metyl-1-(2-hydroxyethyl)-3-imidazolio, 1-quinuclidinio, 4-carbamoyl-1-quinuclidinio, 1-methyl-1-pyrrolidinio; or a mercapto group substituted with a furyol, thenoyl group or with an optionally substituted heterocycle radical such as 1-methyltetrazol-5-yl, 1-sulfomethyltetrazol-5-yl, 1-(2-dimethylaminoethyl)tetrazol-5-yl, thiazol-2-yl, 5-carboxymethyl-4-methylthiazol-2-yl, 5-methyl-1,3,4-thiadiazol-2-yl, 1 H-1,2,3-triazol-4-yl, 1H-1,2,4-triazol-3-yl, 5-methyl-1,3,4-thiadiazol-2-yl, 1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl. Mainly, the acyl group is an optionally substituted phenylacetyl, α-(optionally N-substituted)aminophenylacetyl, α-sulfophenylacetyl, α-(optionally O-substituted)hydroxyphenylacetyl (particularly mandeloyl), cyanoacetyl, thienylacetyl, trifluormethylthioacetyl, cyanomethylthioacetyl, (3,5-dichloro-4-oxo-4H-pyrid-1-yl)acetyl, tetrazol-1-ylacetyl, (2-aminothiazol-4-yl)acetyl, 2-(2-aminothiazol-4-yl)-2-(optionally O-protected)oxyiminoacetyl, 2-(5-aminol,2,4-thiadiazol-3-yl)-2-(optionally O-protected)oxyiminoacetyl, S-cysteinylacetyl, thien-2-ylacetyl.
More particularly, the so-called “third-generation-cephalosporins” generally consist of 3-methyl-3-cephem-4-carboxylic acid derivatives substituted in the 7β-position by an α-(2-aminothiazol-4-yl)-α-hydroxyiminoacetamido group, in which the hydroxy group is free or On-substituted with an alkyl group, optionally substituted by a carboxy group, and substituted on the methyl group in the 3-position with the residue of a nucleophilic compound.
The above mentioned third-generation-cephalosporins have been described for the first time in the published German application DE 2556736 (corresponding to U.S. Pat. No. 5,583,216) and, principally, are compounds encompassed by the general formula A wherein R4 is the residue of a nucleophilic compound and R5 is a hydroxy group which may be protected, including their pharmaceutically acceptable esters, the respective salts and the relative solvates
Among these third-generation-cephalosporins, the 7β-[α-(2-aminothiazol-4-yl)-α-hydroxyimino]acetamido-3-methyl-3-cephem-4-carboxylic acid derivatives of formula A, in which R5 is methoxy and R4 is a 2-furoylthio group (ceftiofur), an acetoxy group (cefotaxime) or a,1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-ylthio group (ceftriaxone) are particularly interesting compounds.